Building a Synthesis Machine

I3. Building a Synthesis Machine.

Aim: To establish a group with the necessary skills, and to seek funding, to build a demonstration ‘synthesis machine’.

To drive development, and establish a high profile for the UK in the emerging area of automated synthesis of small molecules we believe that a limited ‘Dial-a-Molecule’ system should be built. The initial aim might be a system which can rapidly and reliably deliver a small quantity of any one of 10^n diverse small molecules (e.g. n = 9, a billion) (with the opportunity to increase n as a driver for future work). For comparison the National Compound Collection initiative produced a virtual library of 75k compounds which have been synthesized in UK academia, and is considered valuable <Chem. Sci. 2016 DOI: 10.1039/C6SC00264A>. It will be critical for the library to be highly diverse, with a bias towards complex 3D frameworks and ‘drug like’ molecules, although a strand directed towards materials applications is also important. It needs to bring together many of the advances being targeted in T1-T3 such as synthetic technologies(3.3-3.7), hardware for sequencing them (T2.2-2.7), and crucially software to ensure that synthetic sequences will produce the desired outcome (T1.5). Establishing if there is currently (or will be in the foreseeable future) a sustainable business case for such a virtual library of deliverable compounds is important. The key determinant is how effective virtual screening is at predicting biological (or other useful) properties. If it is good enough then the extra cost of synthesis of a specific molecule identified from a virtual library, as opposed to screening larger, but per molecule much cheaper, libraries, is justified. We will hold meetings to determine the interested parties, approach, viability, scope and potential funding for such an initiative.